Interpretive Summary: Caffeic acid and 5-caffeoylquinic acid (a chlorogenic acid) are a naturally occurring phenolic acid and its ester found in human diets that include coffee (Coffea arabica). Caffeic acid and 5-caffeoylquinic acid are reported to decrease the risk of human chronic diseases such as inflammation, cardiovascular disease, and cancer. Platelet activation and consequent biological events are major risk factors in the development of several cardiovascular and inflammatory diseases such as atherosclerosis, angina, acute myocardial infarction, and ischemic cerebral stroke. P-selectin is a bio-marker membrane protein expressed on platelets. Due to significant association of P-selectin with coronary artery disease and stroke, compounds able to decrease P-selectin presence on platelets have been explored. In this study, potential effects of caffeic acid and 5-caffeoylquinic acid on P-selectin expression were investigated in this study using in vitro and in vivo models, and the acids were found to suppress P-selectin via inhibiting COX enzymes in platelets. The outcomes of this study will provide researchers in nutrition, molecular biology, and medical fields new information regarding the roles of dietary caffeic acid and 5-caffeoylquinic acid in possibly reducing the risks of human chronic diseases (e.g., inflammatory and cardiovascular disease).

Technical Abstract:
Caffeic acid and 5-caffeoylquinic acid are a naturally occurring phenolic acid and its ester found in human diets. In this paper, potential effects of caffeic acid and 5-caffeoylquinic acid found in coffee and other plant sources on platelet activation were studied via investigating P-selectin expression on platelets in mice. First, the effects of caffeic acid and 5-caffeoylquinic acid on COX I and II enzymes were investigated, because COX enzymes are deeply involved in regulating P-selectin expression on platelets. At the concentration of 0.05 uM, both 5-caffeoylquinic acid and caffeic acid were potent compounds able to inhibit COX-I enzyme activity by 63% (P < 0.013) and 69% (P < 0.013), respectively. At the same concentration, 5-caffeoylquinic acid and caffeic acid were also able to inhibit COX-II enzyme activity by 59% (P < 0.015) and 64% (P < 0.015). As expected, 5-caffeoylquinic acid and caffeic acid at the concentration of 0.05 uM were able to inhibit P-selectin expression on the platelets by 33% (P < 0.011) and 35% (P < 0.011), respectively. In animal studies, P-selectin expression was moderately reduced by 22% (P < 0.011) and 41% (P < 0.011) in the plasma samples from mice orally administered 5-caffeoylquinic acid (400ug per 30g body weight) and caffeic acid (50ug per 30g body weight), respectively. These data suggest that both 5-caffeoylquinic acid and caffeic acid orally administrated are able to suppress P-selectin expression on mouse platelets.